The present invention pertains to novel stains of lactic acid bacteria that are capable to reduce an individual's tendency to develop allergic reactions. In particular, the present invention relates to novel strains of lactic acid bacteria that express polypeptides including tolerogenic peptides and the use thereof in reducing an individual's tendency to develop allergic reactions. The invention also pertains to food or pharmaceutical compositions containing said micro-organisms or active fractions thereof.
Allergies are inappropriate reactions of the immune system to a variety of substances (allergens). Generally, individuals do not generate a substantial immune reaction against substances regularly encountered in the environment, such as pollen or food material, which non-reactivity is deemed to be mainly due to a suppressing mechanism of the immune system itself. However, in an impaired condition the immune system does not fulfil said suppressing activity (designated tolerance) resulting in a specific immune reaction against the allergen—the allergic reaction. Allergic reactions involve the release of biologically active compounds, such as the inflammation mediators histamine, leukotrienes and enzymes, from particular cells, mainly mast cells and basophil granulocytes, into surrounding tissue and vascular structures. Mast cells are dispersed throughout the individuals tissue whilst basophils circulate within the vascular system. Upon a sequence of events involving IgE antibodies the compounds/mediators are released from target mast cells ending up in pharmacological reactions.
In the past, the number of individuals suffering from allergy has increased, which is often attributed to an ever increasing atmospheric pollution caused by e.g. exhaust gases. Also, an extended consumption of proteinaceous material is deemed to contribute to said development, in particular to the growing occurrence of food allergy. In addition, the deficit in microbial infections encountered in developed countries has been suggested as another possible cause for the increase of atopic diseases.
Food allergies and even food intolerance of some kind have become quite common. The majority of the affected individuals have been found to exhibit an intolerance to certain constituents of foods with about 5 percent of the population even developing reactions to ingested substances which are sufficiently serious to require medical attention.
In recent years evidence has mounted that the major cause for food intolerance resides in the absorption of substances by the body that are normally excluded, which are, however, absorbed by the gastrointestinal tract in susceptible individuals. This mal-absorption is deemed to derive from defects in the tissue which lines the digestive tract (Peters et al., (1988) Can. J. of Gastroenterol. 2, 127; Olaison et al., (1990) Scand. J. of Gastroenterol. 25, 321; Hollander et al., (1986) Ann. of Int. Med. 105, 883). The recently identified capacity of epithelial cells lining the GI tract to process and present antigens might also account for the triggering of improper immune reactions leading to an inflammation and allergic outcome (Campbell et al., (1999) Immunol. Rev. 172, 315).
The manifestation of food allergy may involve substantially any tissue in the body. Because of its large absorptive area the gastrointestinal tract is likely to be the major site of absorption for offending substances. Many of the symptoms of food allergies are manifest in the digestive tract itself, but might also affect other tissues, including the skin and airways.
In the art different approaches are proposed to treat allergy, in particular food allergy.
One such approach aims at modifying the source of the allergenic material itself such that its allergic potential is reduced. This may be achieved by limiting or banning the food or components thereof, respectively, which would be the cause of such problems. A problem involved often resides in that the specific antigenic substance (allergen) in the respective food material is frequently not known so that in most cases it is not clear which component should be selectively removed.
In U.S. Pat. No. 5,480,660 is reported that the onset of the allergy in patients with allergies to wheat may be alleviated by eliminating or reducing, from flour, proteins having molecular weights of not more than 30,000 Da and proteins having a molecular weight of between 50,000 to 70,000 Da
In JP 11 04 67 21 there is disclosed a method for reducing the allergeneicity of a protein containing food material, wherein the food material is mixed with wheat flour and the mixture is baked for more than 3 minutes at 180° C.
In U.S. Pat. No. 4,293,571 the preparation of a hypoallergenic composition is described, wherein a proteinaceous material is subjected to a hydrolysis treatment, the remaining, non hydrolysed proteins are subjected to coagulation by heat treatment followed by an ultrafiltration step to eliminate the coagulated material and macropeptides that might constitute allergens.
In U.S. Pat. No. 5,039,532 another process for the preparation of hypoallergenic food material is disclosed, wherein a whey product is subjected to enzymatic hydrolysis.
Yet, all these methods of treating the food material or even excluding it from the daily diet eventually prove to be difficult in practice, since they require diet revision, usually involving strict restrictive measures and may eventually affect the quality of life and/or inhibit the expected growth of the individual.
A different approach of treating food allergy and food intolerance is directed to restoring and maintaining the intestine's integrity such that food allergens essentially may not pass. In this respect U.S. Pat. No. 5,192,750 describes the use of N-acetyl glucosamine to enable the mucosa to form the necessary barrier to transmission of food allergens and to maintain normal function.
According to yet another approach of treating allergy vaccination of individuals against IgE molecules is suggested which inhibits the triggering of mast cells and basophils. To this end, WO 97/31948 proposes specific peptides for vaccination that resemble in their three dimensional conformation parts of the IgE molecule, immunoglobulins involved in the release of the mediators involved in the regulation of allergic and inflammatory reactions. It is conceived that the individual's own immune system will eventually form antibodies directed to said IgE molecules such that said IgE immunoglobulins are scavenged. However, said method harbors the disadvantage the antibodies formed may exhibit cross-reactivity with other immunoglobulin classes, such that the natural defence mechanisms of the individual may be adversely influenced.
In EP 99200130.5, a patent application owned by the present applicant, which has not yet been published, still another approach is disclosed. A hypoallergenic composition is proposed that contains a non-allergenic, extensively hydrolysed protein material and/or a free amino acid basis and at least one tolerogenic peptide of the respective allergenic protein. Although this composition provides many advantages over the prior art it is still difficult to obtain the tolerogenic peptide, which has to be produced for each batch de novo.